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Choroideremia
This rare eye disorder causes night blindness in childhood followed by gradual loss of peripheral and central vision. The condition results from variants in CHM, which encodes a protein essential for maintaining photoreceptor and retinal cells. The condition predominantly affects males, who inherit the pathogenic variant from their mothers; carrier females may show milder symptoms or remain unaffected.
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Overview
Choroideremia is a rare inherited retinal dystrophy characterised by the gradual breakdown of three key eye structures: the choroid (a vascular layer supplying nutrients to the retina), the retinal pigment epithelium (cells that support photoreceptors), and the photoreceptors themselves (light-sensing cells essential for vision). Because CHM is located on the X chromosome, the condition follows X-linked recessive inheritance, meaning affected individuals are typically males who inherit a single pathogenic variant from carrier mothers. Prevalence estimates suggest approximately 1 in 50,000 to 100,000 people carry a diagnosis [PMID:28467908].
Initial signs often appear during childhood or adolescence, with impaired vision in dim lighting and narrowing side vision being common early presentations. The visual field contracts progressively over decades, and central vision may decline in mid to later adulthood. Rates of progression differ markedly among affected individuals, even within the same family sharing identical genetic variants [PMID:31427686]. Males are predominantly affected, whilst carrier females may experience mild symptoms or retain normal vision throughout life [PMID:28467908].
Symptoms & clinical features
The hallmark early symptom of choroideremia is difficulty seeing in poorly lit environments, often termed night blindness or nyctalopia. This typically emerges during childhood or teenage years, when affected individuals may struggle to navigate dimly lit rooms or need prolonged adaptation time when moving from bright to dark surroundings. As years progress, side vision contracts steadily, creating a tunnel vision effect where peripheral awareness shrinks gradually [PMID:28467908].
Central vision - necessary for tasks like reading, recognising faces, and detailed work - often remains relatively preserved until later decades, sometimes lasting into the fifth or sixth decade of life. However, timelines show considerable variation: some individuals maintain functional central vision into their sixties or later, whilst others experience earlier decline. Perception of colour typically stays intact until advanced stages. During eye examination, distinctive changes appear as irregular patches where retinal pigment has vanished, exposing underlying blood vessels and creating a pale or mottled pattern at the back of the eye.
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Affected organs
Choroideremia exclusively affects the eye, with degeneration concentrated in the posterior segment. The choroid, a highly vascularised layer beneath the retina, becomes progressively thinner and atrophic, reducing blood supply to structures above it. The retinal pigment epithelium, essential for nourishing photoreceptors and removing metabolic waste, also breaks down. Consequently, photoreceptors - rods (enabling peripheral and low-light vision) and cones (providing central and colour vision) - gradually lose function and die [PMID:31427686]. Eye examination typically shows irregular loss of pigment with choroidal vessels visible underneath. No other organ systems are known to be involved in choroideremia.
Risks & severity
Individuals with choroideremia experience progressive visual impairment, though the pace differs between affected people. Many preserve some functional central vision into their forties or fifties, but legal blindness - defined by specific visual acuity and field criteria - commonly develops by the fifth to seventh decade [PMID:28467908]. Some maintain limited central vision even longer, whilst others progress more rapidly.
The severity spectrum appears influenced by the specific CHM variant and possibly by modifier genes or environmental factors, though these elements remain incompletely characterised. Regular ophthalmology monitoring helps track individual progression and guide supportive interventions tailored to functional visual status at each stage.
Genetic causes
Choroideremia results from pathogenic variants in CHM, located on the X chromosome at position Xq21.2. This gene encodes Rab escort protein-1, abbreviated REP-1, which coordinates a cellular mechanism known as protein prenylation. REP-1 assists in attaching lipid molecules to Rab proteins, a family of molecular regulators that control how materials move between different compartments within cells [PMID:31427686]. In photoreceptors and retinal pigment epithelium, efficient cargo transport between organelles is critical for maintaining the complex structures and high metabolic activity required for vision.
When pathogenic alterations disrupt CHM, REP-1 activity becomes reduced or entirely absent. This failure in Rab protein processing compromises intracellular trafficking, undermining cellular functions necessary for photoreceptor survival and retinal pigment epithelium maintenance. These cells gradually degenerate, and choroidal atrophy follows. A related protein, REP-2, can partially compensate in some tissues but cannot adequately support retinal cells, explaining why damage is limited to the eye [PMID:28467908]. Most disease-causing variants in CHM are loss-of-function changes, including nonsense variants, frameshifts, or deletions, though missense variants impairing protein stability or function also occur.
- CHM CHM Rab escort proteinThe CHM gene contains instructions for making Rab escort protein-1 (REP-1), a crucial protein involved in cellular trafficking.
Inheritance pattern
Choroideremia follows X-linked recessive inheritance because CHM is located on the X chromosome. Males have one X chromosome and one Y chromosome, so a single pathogenic variant in CHM causes the condition. Females have two X chromosomes; most carrier females - those with one pathogenic variant and one working copy - show minimal or no symptoms because the working copy on the second X chromosome provides sufficient REP-1 protein. However, some carrier females may experience mild night blindness or patchy retinal changes due to random X-inactivation patterns [PMID:28467908].
When a carrier mother has children, each son has a 50% chance of inheriting the pathogenic variant and being affected, and each daughter has a 50% chance of inheriting the variant and becoming a carrier. Affected males will pass the pathogenic variant to all their daughters (who become carriers) but to none of their sons (who receive the father's Y chromosome). Genetic counselling can clarify individual family risks, discuss carrier testing for female relatives, and explore options such as predictive testing or prenatal/preimplantation genetic diagnosis for families planning pregnancies.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of choroideremia typically begins with clinical evaluation by an ophthalmologist or optometrist, often prompted by symptoms such as night blindness or abnormal findings during routine eye examinations. Fundus examination shows distinctive changes: irregular loss of retinal pigment epithelium, visible choroidal vessels beneath, and progressive thinning. Imaging techniques including fundus autofluorescence and optical coherence tomography (OCT) help document the extent of degeneration and monitor progression over time [PMID:31427686].
Confirmation requires molecular genetic testing to identify pathogenic variants in CHM. Within the UK, testing is accessed via NHS clinical genetics services. Patients meeting clinical criteria may be referred by their ophthalmologist or GP to a regional genetics centre. The NHS Genomic Medicine Service includes choroideremia within its testing portfolios, and the relevant PanelApp virtual gene panel (R32 for inherited retinal disorders) includes CHM. Genetic confirmation enables precise diagnosis, informs reproductive planning, and permits access to research studies and emerging therapies. Carrier testing for female relatives and predictive testing for at-risk family members can be arranged through genetic counselling.
Management & lifestyle
No cure for choroideremia currently exists, so management focuses on maximising remaining vision, providing support, and monitoring for potential complications. Regular ophthalmology appointments are recommended to evaluate disease progression and visual function. Low-vision services can supply aids such as magnifiers, high-contrast materials, and mobility training to assist individuals as vision declines. Patients are often advised to avoid smoking and maintain cardiovascular health, though specific dietary interventions lack strong evidence in choroideremia [PMID:28467908]. No dietary supplement has been shown to prevent or slow choroideremia progression; discuss any supplements with your healthcare provider before starting them.
Gene therapy trials for choroideremia have demonstrated promising outcomes, with some participants experiencing stabilisation or modest vision improvement. These experimental interventions involve delivering a functional CHM copy directly into retinal cells using a viral vector. Whilst not yet standard NHS care, affected individuals may qualify for clinical trials at specialist centres. Patients interested in such approaches should discuss options with their ophthalmologist or genetic counsellor. Psychological support and connection to patient organisations, such as Choroideremia Research Foundation UK, can provide valuable practical guidance and community links for affected individuals and families.
UK care pathway
In the UK, patients with suspected choroideremia are typically referred to an ophthalmologist specialising in inherited retinal disorders. Following clinical evaluation, referral to a regional NHS genetics service enables genetic testing via the NHS Genomic Medicine Service. Choroideremia is covered under test directory code R32 (inherited retinal disorders) on NHS PanelApp. Genetic confirmation provides access to genetic counselling, family cascade testing, and enrolment in research registries maintained by specialist centres or charities.
Ongoing care usually involves ophthalmology follow-up at intervals determined by disease stage, commonly annually or biennially. Low-vision services, available through NHS or local authorities, offer practical daily living support. As gene therapy research progresses, specialist inherited retinal disease centres - such as those in Oxford, London, and Manchester - may offer trial participation or, eventually, approved treatments. Patients should maintain contact with their clinical genetics team to receive updates on emerging therapies and care pathways.
Frequently asked questions
Will my vision loss from choroideremia be the same as my affected relative's?
Not necessarily. Even within the same family, the rate of vision loss can vary, with some individuals retaining useful central vision longer than others. Factors influencing progression are not fully understood, but regular monitoring helps track your specific course.
How is choroideremia inherited in my family?
Choroideremia follows X-linked recessive inheritance. Affected individuals are typically males who inherit the pathogenic CHM variant from their carrier mothers. Each son of a carrier mother has a 50% chance of being affected, and each daughter has a 50% chance of being a carrier. A genetic counsellor can explain your family's specific risks and testing options.
Are there treatments available for choroideremia?
Currently, no cure exists, but gene therapy trials have shown encouraging results, with some participants experiencing stabilisation or modest vision improvement. These are not yet routine NHS treatments, but affected individuals may be eligible for clinical trials at specialist centres.
How is choroideremia different from retinitis pigmentosa?
Both cause night blindness and peripheral vision loss, but choroideremia specifically results from CHM variants and shows characteristic choroidal atrophy on examination. Retinitis pigmentosa is a group of conditions with different genes and inheritance patterns, requiring genetic testing to distinguish accurately.
What support is available for daily living as my vision declines?
NHS low-vision services can provide practical aids like magnifiers and mobility training. Patient organisations such as Choroideremia Research Foundation UK offer community support and practical advice. Your ophthalmology team can arrange referrals to these services.
References
- Weisschuh N, Obermaier CD, Battke F. Genetic architecture of inherited retinal degeneration in Germany: A large cohort study from a single diagnostic center over a 9-year period. Human mutation. 2020. PMID: 32531858
- Dimopoulos IS, Radziwon A, St Laurent CD. Choroideremia. Current opinion in ophthalmology. 2017. PMID: 28520608
- Adam MP, Bick S, Mirzaa GM. Choroideremia. 1993. PMID: 20301511
- De Silva SR, Arno G, Robson AG. The X-linked retinopathies: Physiological insights, pathogenic mechanisms, phenotypic features and novel therapies. Progress in retinal and eye research. 2021. PMID: 32860923
- Zhou A, Tsang SH, Sharma T. X-Linked Choroideremia. Advances in experimental medicine and biology. 2025. PMID: 40736811
- Sarkar H, Moosajee M. Choroideremia: molecular mechanisms and therapies. Trends in molecular medicine. 2022. PMID: 35341685
- Cehajic Kapetanovic J, Barnard AR, MacLaren RE. Molecular Therapies for Choroideremia. Genes. 2019. PMID: 31548516
- Abdalla Elsayed MEA, Taylor LJ, Josan AS. Choroideremia: The Endpoint Endgame. International journal of molecular sciences. 2023. PMID: 37762657